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Bone Res

Title:		Skeletal loading regulates breast cancer-associated osteolysis in a loading intensity-dependent fashion
Author(s):		Fan Y; Jalali A; Chen A; Zhao X; Liu S; Teli M; Guo Y; Li F; Li J; Siegel A; Yang L; Liu J; Na S; Agarwal M; Robling AG; Nakshatri H; Li BY; Yokota H;
Address:		"1Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, 150081 China. ISNI: 0000 0001 2204 9268. GRID: grid.410736.7 2Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202 USA. ISNI: 0000 0001 2287 3919. GRID: grid.257413.6 Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730 China. 4Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202 USA. ISNI: 0000 0001 2287 3919. GRID: grid.257413.6 5Department of Mechanical Engineering, Oakland University, Rochester, MI 48309 USA. ISNI: 0000 0001 2219 916X. GRID: grid.261277.7 6Integrative Nanosystems Development Institute, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202 USA. ISNI: 0000 0001 2287 3919. GRID: grid.257413.6 7Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202 USA. ISNI: 0000 0001 2287 3919. GRID: grid.257413.6 8Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN 46202 USA. ISNI: 0000 0001 2287 3919. GRID: grid.257413.6 9Department of Surgery, Simon Cancer Research Center, Indiana University School of Medicine, Indianapolis, IN 46202 USA. ISNI: 0000 0001 2287 3919. GRID: grid.257413.6"
Journal Title:		Bone Res
Year:		2020
Volume:		20200214
Issue:
Page Number:		9 -
DOI:		10.1038/s41413-020-0083-6
ISSN/ISBN:		2095-4700 (Print) 2095-6231 (Electronic) 2095-4700 (Linking)
Abstract:		"Osteocytes are mechanosensitive bone cells, but little is known about their effects on tumor cells in response to mechanical stimulation. We treated breast cancer cells with osteocyte-derived conditioned medium (CM) and fluid flow-treated conditioned medium (FFCM) with 0.25 Pa and 1 Pa shear stress. Notably, CM and FFCM at 0.25 Pa induced the mesenchymal-to-epithelial transition (MET), but FFCM at 1 Pa induced the epithelial-to-mesenchymal transition (EMT). This suggested that the effects of fluid flow on conditioned media depend on flow intensity. Fluorescence resonance energy transfer (FRET)-based evaluation of Src activity and vinculin molecular force showed that osteopontin was involved in EMT and MET switching. A mouse model of tumor-induced osteolysis was tested using dynamic tibia loadings of 1, 2, and 5 N. The low 1 N loading suppressed tumor-induced osteolysis, but this beneficial effect was lost and reversed with loads at 2 and 5 N, respectively. Changing the loading intensities in vivo also led to changes in serum TGFbeta levels and the composition of tumor-associated volatile organic compounds in the urine. Collectively, this study demonstrated the critical role of intensity-dependent mechanotransduction and osteopontin in tumor-osteocyte communication, indicating that a biophysical factor can tangibly alter the behaviors of tumor cells in the bone microenvironment"
Keywords:		Bone cancer;
Notes:		"PubMed-not-MEDLINEFan, Yao Jalali, Aydin Chen, Andy Zhao, Xinyu Liu, Shengzhi Teli, Meghana Guo, Yunxia Li, Fangjia Li, Junrui Siegel, Amanda Yang, Lianxiang Liu, Jing Na, Sungsoo Agarwal, Mangilal Robling, Alexander G Nakshatri, Harikrishna Li, Bai-Yan Yokota, Hiroki eng IK6 BX003783/BX/BLRD VA/ R01 AR052144/AR/NIAMS NIH HHS/ R01 AR053237/AR/NIAMS NIH HHS/ R03 CA238555/CA/NCI NIH HHS/ China 2020/03/05 Bone Res. 2020 Feb 14; 8:9. doi: 10.1038/s41413-020-0083-6. eCollection 2020"